TY - JOUR
T1 - Optimal trough concentration of voriconazole with therapeutic drug monitoring in children
T2 - A systematic review and meta-analysis
AU - Hanai, Yuki
AU - Hamada, Yukihiro
AU - Kimura, Toshimi
AU - Matsumoto, Kazuaki
AU - Takahashi, Yoshiko
AU - Fujii, Satoshi
AU - Nishizawa, Kenji
AU - Takesue, Yoshio
N1 - Funding Information:
Y. Takesue has received grant support from Sumitomo Dainippon Pharma Co., 322 Ltd, and Shionogi & Co., Ltd. and payment for lectures from Astellas Pharma Inc. and 323 MSD Japan. Y. Hamada has received speaker honoraria from Pfizer Japan Inc. The other authors have no conflict of interest to declare.
Funding Information:
This research was supported by the Agency for Medical Research and Development (AMED) under Grant Number JP18fk0108045 . The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript.
Publisher Copyright:
© 2020 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases
PY - 2021/2
Y1 - 2021/2
N2 - Objectives: This systematic review and meta-analysis was designed to determine the optimal trough concentration of voriconazole for children with invasive fungal infections (IFIs). Methods: We searched electronic databases (PubMed, Cochrane Central Register of Controlled Trials, ClinicalTrials.gov and Japana Centra Revuo Medicina) for clinical studies describing the voriconazole trough concentration. We used stepwise cut-off values of 1.0–2.0 mg/L for efficacy and 3.0–6.0 mg/L for safety. The efficacy outcomes were treatment success and all-cause mortality, and the safety outcomes were hepatotoxicity, neurotoxicity and all-cause adverse events. Results: Nine studies involving 211 patients were included in the analysis. The probability of treatment success against IFIs was significantly increased at cut-off values of ≥1.0 mg/L (odds ratio [OR] = 2.65, 95% confidence interval [CI] = 1.20–5.87). Our analysis did not find any relationship between the trough concentration and survival. Concerning safety, the occurrence of any outcomes did not significantly differ according to the voriconazole trough concentrations at any cut-off value. However, in a subgroup analysis of Asian study locations, a significantly higher risk of hepatotoxicity was demonstrated at voriconazole trough cut-off values ≥ 3.0 mg/L (OR = 8.40, 95% CI = 1.36–51.92). Although a significant correlation between the voriconazole concentration and hepatotoxicity was evident in regression curve analysis, (y = 0.1198e0.2298x), no correlation was demonstrated for neurotoxicity (y = 0.3913e−0.008x). Conclusion: Our findings suggest that the optimal trough concentration for increasing clinical success and minimizing hepatotoxicity during voriconazole therapy in children with IFIs, particularly for Asian populations, is 1.0–3.0 mg/L.
AB - Objectives: This systematic review and meta-analysis was designed to determine the optimal trough concentration of voriconazole for children with invasive fungal infections (IFIs). Methods: We searched electronic databases (PubMed, Cochrane Central Register of Controlled Trials, ClinicalTrials.gov and Japana Centra Revuo Medicina) for clinical studies describing the voriconazole trough concentration. We used stepwise cut-off values of 1.0–2.0 mg/L for efficacy and 3.0–6.0 mg/L for safety. The efficacy outcomes were treatment success and all-cause mortality, and the safety outcomes were hepatotoxicity, neurotoxicity and all-cause adverse events. Results: Nine studies involving 211 patients were included in the analysis. The probability of treatment success against IFIs was significantly increased at cut-off values of ≥1.0 mg/L (odds ratio [OR] = 2.65, 95% confidence interval [CI] = 1.20–5.87). Our analysis did not find any relationship between the trough concentration and survival. Concerning safety, the occurrence of any outcomes did not significantly differ according to the voriconazole trough concentrations at any cut-off value. However, in a subgroup analysis of Asian study locations, a significantly higher risk of hepatotoxicity was demonstrated at voriconazole trough cut-off values ≥ 3.0 mg/L (OR = 8.40, 95% CI = 1.36–51.92). Although a significant correlation between the voriconazole concentration and hepatotoxicity was evident in regression curve analysis, (y = 0.1198e0.2298x), no correlation was demonstrated for neurotoxicity (y = 0.3913e−0.008x). Conclusion: Our findings suggest that the optimal trough concentration for increasing clinical success and minimizing hepatotoxicity during voriconazole therapy in children with IFIs, particularly for Asian populations, is 1.0–3.0 mg/L.
KW - Children
KW - Meta-analysis
KW - Therapeutic drug monitoring
KW - Voriconazole
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U2 - 10.1016/j.jiac.2020.11.014
DO - 10.1016/j.jiac.2020.11.014
M3 - Review article
C2 - 33376032
AN - SCOPUS:85098647786
VL - 27
SP - 151
EP - 160
JO - Journal of Infection and Chemotherapy
JF - Journal of Infection and Chemotherapy
SN - 1341-321X
IS - 2
ER -